The overall objective of this proposal is to develop a solid experimental basis for new, clinically useful proton magnetic resonance (MR) techniques which are applicable to the diagnosis of demyelination and other white matter diseases. Our preliminary research suggests that MR will provide an accurate diagnosis in some, and clinically essential information in most, of the diseases characterized by the presence of abnormal myelin in the nervous system. Our specific aims include: to explain the white-gray matter contrast in MR images; to compare the role of water and lipid protons in characterizing normal and abnormal white matter; to determine the influence of myline membranes on tissue water relaxation. By studying the progress of myelination during brain maturation and by experimentally manipulating the water distribution in myelin-associated biological compartments we hope to characterize those physical compartments which determine the relaxation of normal and abnormal white matter. Finally, we plan to develop new spectroscopic and imaging MR techniques which yield precise information about the natural course of demyelination and allow the early detection of white matter diseases before the process of demyelination is apparent by the already known standard MR imaging methods. Our preliminary results suggest that there is a potential to measure relaxation rates of small water sub-compartments by multiexponential fitting of the decay of magnetization. This represents a significant increase in the sensitivity of MR to white matter pathology when compared to MR analysis based upon the assumption of mono-expotential relaxation.